Summary Tuberculosis (TB) along with acquired immune deficiency syndrome and malaria rank among the top three fatal infectious diseases which pose threat to global public health, especially in middle and low income countries. TB caused by Mycobacterium tuberculosis (Mtb) is an airborne infectious disease and one‐third of the world's population gets infected with TB leading to nearly 1·6 million deaths annually. TB drugs are administered in different combinations of four first‐line drugs (rifampicin, isoniazid, pyrazinamide and ethambutol) which form the core of treatment regimens in the initial treatment phase of 6–9 months. Several reasons account for the failure of TB therapy such as (i) late diagnosis, (ii) lack of timely and proper administration of effective drugs, (iii) lower availability of less toxic, inexpensive and effective drugs, (iv) long treatment duration, (v) nonadherence to drug regimen and (vi) evolution of drug‐resistant TB strains. Drug‐resistant TB poses a significant challenge to TB therapy and control programs. In the background of worldwide emergence of 558 000 new TB cases with resistance to rifampicin in the year 2017 and of them, 82% becoming multidrug‐resistant TB (MDR‐TB), it is essential to continuously update the knowledge on the mechanisms and molecular basis for evolution of Mtb drug resistance. This narrative and traditional review summarizes the progress on the anti‐tubercular agents, their mode of action and drug resistance mechanisms in Mtb. The aim of this review is to provide recent updates on drug resistance mechanisms, newly developed/repurposed anti‐TB agents in pipeline and international recommendations to manage MDR‐TB. It is based on recent literature and WHO guidelines and aims to facilitate better understanding of drug resistance for effective TB therapy and clinical management.

Over the past few decades nanotechnology and material science has progressed extremely rapidly. Iron oxide nanoparticles (IONPs) owing to their unique magnetic properties have a great potential for their biomedical and bioengineering applications. However, there is an inevitable need to address the issue of safety and health effects of these nanoparticles. Hence, the present study was aimed to assess the cytotoxic effects of IONPs on rats' lymphocytes. Using different assays, we studied diverse parameters including mitochondrial membrane potential, intracellular accumulation of reactive oxygen species (ROS), lactate dehydrogenase activity, antioxidant enzymes activity and DNA damage measurements. Intracellular metal uptake and ultrastructure analysis were also carried out through inductively coupled plasma atomic emission spectroscopy, transmission electron microscopy respectively. The results show that the IONP-induced oxidative stress was concentration-dependent in nature, with significant (P < 0.05) increase in ROS levels, lipid peroxidation level as well as depletion of antioxidant enzymes and glutathione. Moreover, we observed morphological changes in the cell after intracellular uptake and localization of nanoparticles in cells. From the findings of the study, it may be concluded that IONPs induce ROS-mediated cytotoxicity in lymphocytes. Copyright © 2017 John Wiley & Sons, Ltd.

Nanotechnology is a rapidly growing field that has elicited much concern due to a variety of applications in different fields such as industry, medicine, and cosmetics. These developments increase the concern among the general population. Hence, there is an urgent need to explore the possible human health effects of these nanomaterials. The present study is aimed to evaluate the cytotoxic and genotoxic effects of iron oxide nanoparticles (IONPs) in-vivo. In order to study the toxic effects, Wistar rats were administered intravenously with various doses of IONPs (Fe 2 O 3) through caudal vein once in a week for 28 days, and various biochemical assays such as antioxidant enzymes activity (SOD, CAT, and GSH), lipid peroxidation, DNA damage and hematological parameters were evaluated. Genotoxicity was evaluated by comet assay and oxidative stress was measured by antioxidant enzymes. The results reveal that IONPs alter hematological factor such as RBC counts, WBC counts, neutrophils, monocytes and hemoglobin. A dose-dependent inhibition (p < 0.05) of antioxidant enzymes was found, and meanwhile the level of MDA elevated significantly (p < 0.05) in IONPs treated groups in dose-dependent manner; however comet assay results indicate that IONPs did not induce any significant DNA damage. The present study concluded that IONP affects inflammatory response, which induces the oxidative stress and may adversely affect the cellular function.

IntroductionNanoparticles are used worldwide because of their unique properties, with large-scale application in various fields, such as medicine, cosmetics and industries. In view of their widespread use, the potential adverse effects of nanoparticles have become a significant cause for concern, in terms of not only human health and safety but also the environment. The present investigation focused on establishing the bioaccumulation patterns and ultrastructural changes induced by retained iron oxide nanoparticles (IONPs) in various target organs of rats.MethodsTwenty-four male Wistar rats were randomly divided into four groups. Experimental animals were intravenously administered different doses of IONPs (7.5 mg/kg, 15 mg/kg and 30 mg/kg) once in a week for 4 weeks. Urine and feces samples were collected on a daily basis to assess nanoparticle clearance and analyzed via atomic absorption spectroscopy (AAS). At the end of the experiment, rats were euthanized and different organs, including spleen, liver, kidney, lung, heart, testis and brain, were dissected. Bioaccumulation of iron in organs and ultrastructural changes induced by IONPs were determined.ResultsThe maximal concentration of iron was detected in spleen and minimal concentration in the brain. The level of iron accumulation in organs was as follows: spleen>blood>liver>kidney>lung>heart>testis>brain. The excretion profile in urine revealed maximum excretion on the day following administration that was maintained until day 28, whereas the iron content in feces remained high during the first three days after injection. A similar pattern was observed throughout the duration of the experiment. Ultrastructural alterations were detected in spleen, kidney, lung, heart, testis, brain and liver, indicative of cellular damage induced by accumulating nanoparticles in these organs.ConclusionIntravenous administration of IONPs results in ultrastructural changes and dose-dependent bioaccumulation in different organs of rats.

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The application and use of iron oxide nanoparticless (IONPs) in the biomedical field are steadily increasing, although it remains uncertain whether IONPs are safe or should be used with caution.

Cadmium selenium quantum dots (CdSe QDs) with modified surfaces exhibit superior dispersion stability and high fluorescence yield, making them desirable biological probes. The knowledge of cellular and biochemical toxicity has been lacking, and there is little information on the correlation between in vitro and in vivo data. The current study was carried out to assess the toxicity of CdSe QDs after intravenous injection in Wistar male rats (230 g). The rats were given a single dose of QDs of 10, 20, 40, and 80 mg/kg and were kept for 30 days. Following that, various biochemical assays, hematological parameters, and bioaccumulation studies were carried out. Functional as well as clinically significant changes were observed. There was a significant increase in WBC while the RBC decreased. This suggested that CdSe quantum dots had inflammatory effects on the treated rats. The various biochemical assays clearly showed that high dose induced hepatic injury. At a dose of 80 mg/kg, bioaccumulation studies revealed that the spleen (120 g/g), liver (78 g/g), and lungs (38 g/g) accumulated the most. In treated Wistar rats, the bioretention profile of QDs was in the following order: the spleen, liver, kidney, lungs, heart, brain, and testis. The accumulation of these QDs induced the generation of intracellular reactive oxygen species, resulting in an alteration in antioxidant activity. It is concluded that these QDs caused oxidative stress, which harmed cellular functions and, under certain conditions, caused partial brain, kidney, spleen, and liver dysfunction. This is one of the most comprehensive in vivo studies on the nanotoxicity of CdSe quantum dots.